Modulation of gap junction coupling in the vertebrate retina

脊椎动物视网膜间隙连接耦合的调节

• 批准号: 194194-2011
• 负责人: Baldridge, William
• 金额: $ 2.26万
• 依托单位: Dalhousie University
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2015
• 资助国家: 加拿大
• 起止时间: 2015-01-01 至 2016-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=569747
• 关键词: Modulation; gap; junction; coupling; vertebrate

The vertebrate retina is a thin sheet of central nervous system tissue lining the back of the eye that transduces the image of the visual world into an electrochemical signal and processes this signal generating parallel pathways encoding different aspect of the visual scene. Gap junctions, the structural correlate of direct electrical coupling between cells, are important participants in the circuitry of the vertebrate retina. The following research focuses on two different aspects of gap junction coupling in the vertebrate retina. First, we propose to continue our studies of the modulation of retinal horizontal cell coupling in the teleost retina by focusing on a potential new source of the neuromodulator dopamine. Second, we will further our study of the coupling of a new type of ganglion cell, the intrinsically light-sensitive, melanopsin-containing ganglion cells, in the mammalian retina. Dopamine (DA) is the best-known neuromodulator of horizontal cell activity. Until recently, the only known source of endogenous dopamine in the teleost retina was interplexiform cells. A possible additional source of DA in the retina has recently been identified. This source is the retinal pigmented epithelium (RPE), where the DA precursor L-DOPA could be synthesized by tyrosinase as part of the synthetic pathway associated with the synthesis of the RPE pigment melanin. We intend to study this potential source of DA by examining two known DA- and light-dependent features of the teleost retina, the movement of cones and the coupling of horizontal cells. These studies will use a zebrafish mutant that lacks tyrosinase and goldfish treated with tyrosinase inhibitors and will employ both anatomical and electrophysiological techniques. Previous work suggests that the intrinsic photosensitive retinal ganglion cells (ipRGCs) are gap junction coupled. We have published anatomical evidence that ipRGCs are coupled to a specific class of amacrine cells in the retina. We intend to determine if this coupling can be demonstrated physiologically, using calcium imaging, and will attempt to identify the type of gap junction that ipRGCs express.

脊椎动物视网膜是一层薄薄的中枢神经系统组织，排列在眼睛的后部，将视觉世界的图像转换为电化学信号，并处理该信号，产生编码视觉场景不同方面的平行通路。缝隙连接是细胞间直接电耦合的结构相关物，是脊椎动物视网膜回路的重要参与者。下面的研究集中在脊椎动物视网膜缝隙连接耦合的两个不同方面。首先，我们建议继续我们的研究的调制视网膜水平细胞耦合的硬骨鱼视网膜的神经调节剂多巴胺的一个潜在的新来源。其次，我们将进一步研究哺乳动物视网膜中一种新型神经节细胞的耦合，这种神经节细胞本质上是光敏的，含有黑视蛋白。 多巴胺（DA）是最著名的水平细胞活动的神经调质。直到最近，硬骨鱼视网膜中内源性多巴胺的唯一已知来源是网间细胞。最近已经确定了视网膜中DA的一个可能的额外来源。该来源是视网膜色素上皮（RPE），其中DA前体L-DOPA可以通过酪氨酸酶合成，作为与RPE色素黑色素合成相关的合成途径的一部分。我们打算通过研究两个已知的DA和光依赖的硬骨鱼视网膜，视锥细胞的运动和水平细胞的耦合功能来研究DA的这种潜在来源。这些研究将使用缺乏酪氨酸酶的斑马鱼突变体和用酪氨酸酶抑制剂处理的金鱼，并将采用解剖学和电生理学技术。 先前的工作表明，视网膜内光敏神经节细胞（ipRGC）是缝隙连接耦合的。我们已经发表了解剖学证据表明ipRGC与视网膜中特定类别的无长突细胞偶联。我们打算确定这种耦合是否可以在生理上证明，使用钙成像，并将试图确定ipRGC表达的间隙连接的类型。